The Effect of Hypothermia on Myogenic Motor-Evoked
Potentials to Electrical Stimulation with a Single Pulse and a
Train of Pulses Under Propofol/Ketamine/Fentanyl
Anesthesia in Rabbits
Takanori Sakamoto, MD, Masahiko Kawaguchi, MD, Meiko Kakimoto, MD, Satoki Inoue, MD,
Masahiro Takahashi, MD, and Hitoshi Furuya, MD
Department of Anesthesiology, Nara Medical University, Japan
In the present study, we investigated the effect of hypo-
thermia on myogenic motor-evoked potentials (MEPs)
in rabbits. The influence of stimulation paradigms to
induce MEPs was evaluated. Twelve rabbits anesthe-
tized with ketamine, fentanyl, and propofol were used
for the study. Myogenic MEPs in response to electrical
stimulation of the motor cortex with a single pulse and a
train of three and five pulses were recorded from the
soleus muscle. After the control recording of MEPs at
38°C of esophageal temperature, the rabbits were
cooled by surface cooling. Esophageal temperature was
maintained at 35°C, 32°C, 30°C, and 28°C, and MEPs
were recorded at each point. MEP amplitude to single-
pulse stimulation was significantly reduced with a re-
duction of core temperature to 28°C compared with the
control value at 38°C (0.8
0.4 mV versus 2.3
0.3 mV;
P  0.05), whereas MEP amplitude to train-pulse stim-
ulation did not change significantly during the cooling.
MEP latency was increased linearly with a reduction of
core temperature regardless of stimulation paradigms.
In conclusion, these results indicate that a reduction of
core temperature to 28°C did not influence MEP ampli-
tudes as long as a train of pulses, but not a single pulse,
was used for stimulation in rabbits under propofol/
ketamine/fentanyl anesthesia.
(Anesth Analg 2003;96:1692–7)
P araplegia remains a devastating complication ofthoracic and thoracoabdominal aortic surgerywith reported incidence ranging from 5% to 40%
(1). Although the underlying mechanisms of paraple-
gia are multifactorial, intraoperative spinal cord ische-
mia plays a fundamental role. Therefore, an early and
precise detection of spinal cord ischemia should be the
essential key to prevent paraplegia. Myogenic motor-
evoked potential (MEP) is a strong candidate for such
intraoperative monitoring because it provides a method
for monitoring the functional integrity of descending
motor pathways (2). However, myogenic MEPs elicited
by single-pulse stimulation are very sensitive to suppres-
sion by most anesthetics (3–8). Recently, to overcome
anesthetic-induced depression of myogenic MEPs,
multiple-stimulus setups with paired or a train of pulses
for stimulation of the motor cortex have been proposed
(9–15). Several investigators have demonstrated that in-
traoperative MEP monitoring with multipulse stimula-
tion is a useful adjunct to prevent paraplegia after tho-
racoabdominal aortic surgery (16–18).
Investigations in animals have shown that mild to
moderate hypothermia is associated with a substantial
decrease in histological damage in models of spinal
cord ischemia and injury (19–21). Hypothermic ther-
apy has been indicated during procedures such as
thoracoabdominal aortic replacement in which the
spinal cord is susceptible to ischemia and injury (1).
MEP monitoring may therefore be required under
hypothermic conditions during such operations. Al-
though electrophysiological monitoring is highly sen-
sitive to changes in body temperature, data on the
influence of hypothermia on myogenic MEPs are lim-
ited (22–24). This study was therefore conducted to
investigate the effect of hypothermia on myogenic
MEPs in rabbits. To induce MEPs, a single pulse or a
train of three or five pulses were used for stimulation
of motor cortex.
Supported, in part, by Grants in Aid for Scientific Research
(10671439) in Japan.
Accepted for publication February 10, 2003.
Address corresponding and reprint requests to Takanori Saka-
moto, MD, Department of Anesthesiology, Nara Medical Univer-
sity, 840 Shijo-cho, Kashihara, Nara 634–8522, Japan. Address
e-mail to tsakamot@naramed-u.ac.jp.
DOI: 10.1213/01.ANE.0000064202.24119.07
©2003 by the International Anesthesia Research Society
1692 Anesth Analg 2003;96:1692–7 0003-2999/03

Materials and Methods
Twelve male New Zealand white rabbits weighing
2.0–2.5 kg (mean, 2.3 kg) were used in this study. They
were housed and maintained on a 12-h light-dark
cycle with free access to food and water. The study
was approved by the Animal Experiment Committee
of Nara Medical University.
The rabbits were given 50 mg/kg of ketamine IM,
and a 24-gauge catheter was placed in the right mar-
ginal ear vein. Thereafter, a continuous infusion of
25 mg · kg1 · h1 of ketamine and 30
g · kg1 · h1
of fentanyl in lactated Ringer’s solution was initiated
at a rate of 4 mL · kg1 · h1. Another 24-gauge cath-
eter was inserted in the left ear vein for the adminis-
tration of propofol. The trachea was intubated via a
tracheostomy, and the lungs were ventilated mechan-
ically to maintain end-tidal carbon dioxide at 30–
35 mm Hg. End-tidal concentrations of carbon dioxide
were continuously monitored by a gas analyzer
(Hewlett Packard, Andover, MA). The left femoral
artery was exposed and cannulated for arterial blood
pressure monitoring and blood gas analysis. Blood
gases, pH, and hematocrit were measured with a
blood gas analyzer (GEM premier, Mallinckrodt, Ann
Arbor, MI). The values for pH, Pao2, and Paco2 were
not corrected for temperature (-stat management).
The rabbits were turned prone, and the head was
fixed in a stereotactic frame. The scalp was infiltrated
with 1% lidocaine and reflected laterally to expose the
calvarium. Two small craniotomies were performed
with an air drill. A point 0.5 mm lateral to the sagittal
suture and 14.5 mm rostral from the lamboid suture
on the left hemisphere was chosen as an anodal stim-
ulating site. A point 0.5 mm to the right of the sagittal
suture at the level of the lamboid suture was used for
the cathode. Silver ball electrodes (1 mm in diameter)
were placed epidurally via the holes, into which min-
eral oil was applied. Two standard recording needle
electrodes were inserted in the left soleus muscle. A
ground electrode was set at the tail. Constant voltage
anodal stimulation was delivered through an electrical
stimulator (SEN-3301, Nihon Kohden, Tokyo, Japan).
The strength of the electrical stimulus was gradually
increased until the MEP amplitude no longer in-
creased. The recording device (Neuropack sigma; Ni-
hon Kohden, Tokyo, Japan) was triggered by the stim-
ulating device. Low-cutoff and high-cutoff filters were
set at 30 Hz and 3 kHz, respectively. Amplitude was
defined as the voltage from the most negative compo-
nent to the most positive component of the evoked
electromyographic activity. Values were averaged
from three to five individual responses. MEPs in re-
sponse to single-pulse, three-pulse, and five-pulse
stimulations were recorded. The duration of each
pulse was 200
s. The interpulse interval during
multiple-pulse stimulations was set at 2 ms. The in-
terval between successive measurements was 60 s.
After the setting of MEP measurements was com-
pleted, a bolus of 10 mg/kg of propofol was admin-
istered followed by a continuous infusion of propofol
at a rate of 0.8 mg · kg1 · min1. Esophageal temper-
ature was continuously monitored with a thermome-
ter (Mon-a-Therm, Mallinckrodt, St Louis, MO) and
adjusted to 38°C. Thirty minutes after the bolus infu-
sion of propofol, control MEPs were recorded at 38°C.
Then, surface cooling was initiated by irrigating the
water mattress with cold water (4°C). The mattress
was set around the body trunk but was not attached to
the limbs directly. Target esophageal temperatures
were then set at 35°C, 32°C, 30°C, and 28°C. After
target temperature was maintained for 10 min, MEPs
were recorded in the same fashion as described above
at each point. MEP amplitudes were converted to
percentages of the control MEP amplitude (%MEP
amplitude).
To measure the blood concentration of propofol,
blood was collected via an arterial line at each target
temperature in four rabbits. Each blood sample was
immediately centrifuged for 5 min at 3000 rpm. Serum
was stored at 30°C until analysis. On the analysis day,
the samples were defrosted, and then 0.2 mL of each
sample was mixed with 1 mL of ethyl acetate and
0.1 mL of NaOH (50 mM), vortexed vigorously for
5 min, and centrifuged for 5 min at 15,000 rpm. Nine
hundred-microliter aliquots of the supernatants were
freeze-dried. The freeze-dried pellet was resolved
with 0.05 mL of mobile phase and injected unto phe-
nyl reverse-phase column (Micro Bondasphere
5-micro phenyl 100A; Waters Associates, Milford,
MA). The mobile phase (100 mM of phosphate buffer
[pH value of 2.8]; methanol, 6:4) was maintained at a
flow rate of 0.8 mL/min by the high-performance
liquid chromatography pump (655A-11; Hitachi, Ja-
pan). Propofol was detected by a UV-absorbance de-
tector (set at 270 nm; Waters 486; Waters Associates).
After all the recordings, the rabbits were killed by an
injection of potassium chloride, which caused cardiac
arrest.
All values are expressed as mean
sem. For a
statistical analysis, parametrical methods were ap-
plied for all variables because a normal distribution
was confirmed by the Kolmogorov-Smirnov test.
Physiological variables and propofol concentration
were assessed using analysis of variance with re-
peated measurements followed by Student-Newman-
Keuls test for multiple comparisons. %MEP ampli-
tudes and latencies were assessed using two-way
analysis of variance with repeated measurements fol-
lowed by Student-Newman-Keuls test for multiple
comparisons. P value 0.05 was considered to be
significant.
ANESTH ANALG TECHNOLOGY, COMPUTING, AND SIMULATION SAKAMOTO ET AL. 1693
2003;96:1692–7 MOTOR EVOKED POTENTIALS DURING HYPOTHERMIA